The lysis of Gram-negative bacteria
causes them to release lipopolysaccharide (LPS; endotoxin) from the outer membrane
of their cell wall. The LPS binds to a LPS-binding protein circulating in the
blood and this complex, in turn, binds to a receptor molecule (CD14)
found on the surface of body defense cells called macrophages.This
is thought to promote the ability of the pattern recognition receptor (PRR) called TLR-4 to respond
to the LPS, triggering the macrophage to release various defense regulatory
chemicals called cytokines, including IL-1, IL-6, IL-8, TNF-alpha, and PAF.
The cytokines then bind to cytokine receptors on target cells and initiate inflammation
and activate both the complement pathways and the coagulation pathway. LPS can
also bind directly to TLR-4 molecules.